Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial.
Humans
Radiosurgery
/ methods
Carcinoma, Non-Small-Cell Lung
/ pathology
Granulocyte-Macrophage Colony-Stimulating Factor
/ therapeutic use
Male
Female
Lung Neoplasms
/ pathology
Aged
Middle Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Aged, 80 and over
Combined Modality Therapy
Progression-Free Survival
Neoplasm Metastasis
Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 Aug 2024
22 Aug 2024
Historique:
received:
03
03
2024
accepted:
19
08
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
This single-arm, multicenter, phase 2 trial (NCT04106180) investigated the triple combination of sintilimab (anti-PD1 antibody), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic non-small cell lung cancer (NSCLC). With a median follow-up of 32.1 months, 18 (36.7%, 90% CI 25.3%-49.5%) of the 49 evaluable patients had an objective response, meeting the primary endpoint. Secondary endpoints included out-of-field (abscopal) response rate (ASR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). The ASR was 30.6% (95% CI 18.3%-45.4%). The median PFS and OS were 5.9 (95% CI 2.5-9.3) and 18.4 (95% CI 9.7-27.1) months, respectively. Any grade and grade 3 TRAEs occurred in 44 (86.3%) and 6 (11.8%) patients, without grade 4-5 TRAEs. Moreover, in pre-specified biomarker analyses, SBRT-induced increase of follicular helper T cells (Tfh) in unirradiated tumor lesions and patient's blood, as well as of circulating IL-21 levels, was found associated with improved prognosis. Taken together, the triple combination therapy was well tolerated with promising efficacy and Tfh may play a critical role in SBRT-triggered anti-tumor immunity in metastatic NSCLC.
Identifiants
pubmed: 39174542
doi: 10.1038/s41467-024-51807-7
pii: 10.1038/s41467-024-51807-7
doi:
Substances chimiques
Granulocyte-Macrophage Colony-Stimulating Factor
83869-56-1
Antibodies, Monoclonal, Humanized
0
sintilimab
8FU7FQ8UPK
Types de publication
Journal Article
Clinical Trial, Phase II
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
7242Subventions
Organisme : Shanghai Municipal Health Bureau (Shanghai Municipal Public Health Bureau)
ID : 20194Y0501
Informations de copyright
© 2024. The Author(s).
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